PROJECT ABSTRACT Worldwide, about 1.9 million people became infected with HIV in 2015, most of whom live in Southern and Eastern Africa. In South Africa, the HIV incidence rate among female youth aged 15-24 (2.5%) is four times higher than their male counterparts (0.6%). Recent HIV prevention trials in South Africa documented incidence rates of 5-6% per year in 15-24 year old adolescent girls and young women (AGYW). Given this high incidence of HIV, implementing effective HIV prevention strategies ? including PrEP ? is crucial to controlling HIV globally. The proposed study leverages existing community-based HIV counseling and testing platforms in South Africa and evaluates, using a mixed methods approach, a community-based prevention-effective PrEP adherence program in AGYW whilst optimizing the PrEP cascade. This study will take place in the urban Mamelodi Township in Gauteng Provence and rural Govan Mbeki sub-district in Mpumalanga Province, both of which are very high HIV transmission areas. Numerous barriers have been described that delay or block AGYW from accessing clinic-based health services, especially reproductive health and HIV testing and prevention services. Consequently, reaching AGYW at large scale with HIV prevention services requires the health system to think of delivery platforms outside of clinic-based facilities. Community-based counseling and testing programs have shown the greatest coverage and potential to achieve high levels of knowledge of HIV serostatus and linkage to HIV care. Using community-based counseling and testing programs, this proposal will deliver PrEP as part of a population-level combination prevention program which is necessary to substantially reduce HIV incidence. We propose to answer our key research questions through the following Specific Aims: 1) Assess adolescent girls and young women's uptake of PrEP when delivered through large- scale community-based HIV counseling and testing (CBCT) platforms in urban and rural settings in South Africa, 2) Evaluate community-based scalable interventions to achieve prevention-effective adherence to PrEP among AGYW, and 3) Measure differences in risk profiles of PrEP acceptors, non-acceptors and delayed initiators. In order to achieve Aim 1, we will leverage our on-going, at-scale CBCT program and platforms (mobile unit and systematic home-based testing) to identify and link AGYW to community-based PrEP initiation services. In order to achieve Aim 2, we will perform a 3-arm randomized control trial, with participants randomised to one of the following arms: Arm 1) a group-based community health club akin to an ART adherence club; Arm 2) one-on-one adherence counseling and support; Arm 3) community-based medication dispensary. And finally, while PrEP acceptors are being enrolled into the study as part of Aim 1, 516 individuals that decline PrEP will be enrolled as a control group to (a) measure the incidence of STI and HIV infections in PrEP acceptors and non-acceptors, (b): assess sexual behaviors and self- perception risk in those that accept and did not accept PrEP, and (c): determine the proportion of individuals that delay PrEP initiation and describe their reasons for delayed initiation.